Malignant transformation of human melanocytes may be associated with the appearance of a high molecular weight-melanoma associated antigen (HMW-MAA). Since the HMW-MAA meets the criteria to be a useful target for immunotherapy, this proposal aims at evaluating the usefulness of i) heteroconjugates between anti HMW-MAA and anti T3 monoclonal antibodies and of ii) anti HMW-MAA antiidiotype monoclonal antibodies to develop immunotherapeutic approaches to melanoma. Furthermore this proposal aims at broadening the range of specificity of monoclonal antibodies to human melanoma associated antigens (MAA). Since immunization with immune interferon treated melanoma cells has elicited for the first time monoclonal antibodies to MAA with differential distribution in primary and metastatic lesions, we plan to develop monoclonal antibodies utilizing mice immunized with interferon treated melanoma cells. Following an extensive serological and immunochemical characterization the antibodies will be used to characterize surgically removed lesions of melanocyte origin. The in-vitro data will be correlated with the clinical course of the disease. Cell lines and surgically removed tissues will represent the antigen sources. Already available and newly developed hybridomas will represent the antibody sources. Immunochemical, cell mediated immunity and immunohistochemical techniques will represent the assay systems. The results of these studies may suggest new therapeutic approaches to melanoma and may identify new markers to evaluate the biological properties of melanoma cells and the clinical course of the disease.